Pretty pictures

A new technique allows us to take a 3D journey through the mouse brain.

This is the kind of stuff that gets me very excited about science. A new techniques has been developed by researchers in the USA, which allows the brain to becomesee-through‘ leading to numerous opportunities for neuroscience research.

brain

I spent many hours in the lab processing tissue (ie. taking a brain and treating it with chemicals to keep its structure so you can look at it under a microscope). This can be a long and laborious task. The result is hundreds of slides with a small slice of brain on each slide. Therefore to understand the whole brain, many hours are spent on a microscope reconstructing a 3D image.

However, this method has been revolutionised with a new technique called CLARITY, which uses chemicals to make the fatty part of the tissue transparent. Many attempts have been made to develop this technique, but it has been difficult to remove the fatty lipids without affecting the proteins we want to study. This was solved by using the chemical acrylamide, which when heated creates a mesh like structure to protect the important components of the brain.

The resulting images are spectacular. Combining the CLARITY technique with fluorescence technology results in colourful pretty pictures which can help work out how the brain is built and communication occurs between different brain areas. And it is one huge step towards ‘BIG NEUROSCIENCE‘ – the dawning of a new era in neuroscience.

If you don’t believe me, watch this video on a journey to the centre of a mouse’s brain.

Ref:

Full Nature article

 

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A step too far?

A team of scientists have created mouse eggs from stem cells and used them to create baby mice. Is this taking science a step to far? Or is this a huge breakthrough in the field of fertility research?

The experiment started with either embryonic stem cells (found in early stage embryos) or induced pluripotent stem cells (cells taken from adults and modified to develop similar properties of embryonic stem cells) taken from mice. These cells were grown under conditions, which support their growth into oocytes (egg cells) and then transplanted into mice and allowed to develop into mice embryos.

However, the number of healthy offspring was low – only 3.9% of transplanted embryos survived. This may seem very low, but even the control embryos (normal mouse eggs) had a low survival rate of 17.3%. It clearly shows there is still a long way to go before this research comes to fruition.

The implications of this research, if clinically translated to humans, is that women who are infertile will be able to have children who are genetically related to them by using their own stem cells to create eggs. Although this is a plausible idea, the reality is still far away. There are also shorter-term implications of this research, which can be used to study fertility and understand the development of eggs.

This is a fascinating (almost mind-boggling) research concept, which sparked a debate on the issues surrounding ‘frankinstein’ science. Are we playing with nature too much? Would the research money be better spent elsewhere? Or are we taking the same reaction we took when IVF was first announced? I think at these early stages the research is certainly thought provoking and highlights the potential use of stem cells. The day this becomes a reality we will no doubt have different ideas and thoughts on what we should/shouldn’t be doing with nature.

How deadly is Hantavirus?

Mice are wonderful creatures, which have contributed to many scientific discoveries. But they are not always helpful. It is important to remember mice are pests and can pose serious health and safety risks. This was recently highlighted in news emerging from Yosemite National Park of an outbreak of Hantavirus, a virus transmitted by mice.

I’m sure you have seen many of these headlines, but how deadly is Hantavirus?

 

Hantavirus is very rare (602 cases reported in USA in the past 20 years). However, if contracted it can be fatal in one third of cases. Symptoms can take up to 6 weeks to present and include fever, nausea, muscle aches and tiredness.

Hantavirus is spread by droppings and urine from the Deer mouse (Peromyscus maniculatus). Deer mice are found throughout North America. Upto 20% of deer mice carry the Hantavirus.

So far there has been 4 confirmed cases and 2 deaths. Approximately 4 million people visit Yosemite Park every year. Therefore the chances of contracting Hantavirus are very small. However, it is important to be aware of the risks and the initial signs of virus.

The Male Pill

A research study which received massive media coverage this week was the discover of a male contraceptive pill. If this can be successfully translated to humans the impact on society would be incredibly significant. This is why the study received a lot of press.

So what exactly was the experiment? How did they show this works? The scientists used their pharmacology knowledge to develop a drug which targets the production of sperm, which was then tested in mice.

Currently there are no drugs available as a male contraceptive, however, there are a few drugs in clinical trials which alter the amount of testosterone in the body (see NHS website). These drugs are accompanied with some worrying side effects due to the multi functional actions of testosterone in the male body. One of the biggest hurdles so far is a contraceptive pill which retains sexual desire, any hormonal drugs seem to suppress this. However, the drug reported in this study does not primarily target hormones and could therefore be advantageous.

The target of the drug in this study is the bromo- domain-containing protein (BRDT) –  a protein expressed in sperms which is essential for spermatogenesis. A small molecule called JC2 has been developed, which inhibits the activity of BRDT.  The drug JC2 was injected daily into male mice for a period of 3-6 weeks then the mice were allowed to mate with female mice.

The following findings in JC2 treated mice were observed:

– Sperm count was reduced by approximately 28%

– A significant reduction in the size of the testis

 

– Sperm mobility was reduced by approximately 4.5 fold

– The effect was reversible – stopping treatment allowed the mice to breed again

The next step is to try compounds with a higher affinity for BRDT and to study the long term effects of blocking BRDT. The successful translation of the drug from mice to humans is encouraging as BRDT is highly conserved between the two species.

The introduction of a male contraceptive pill will be interesting to follow. A few female comments suggest they wouldn’t trust their partner to be responsible and remember to take the pill. But isn’t it time we gave men the choice?

Further reading:

BBC News ‘Male contraceptive pill ‘step closer’ after mice studies’

The Guardian ‘If you sleep with a man, trust him to take the pill’

Do-re-mi…

Leaving the lab behind, this piece of research uses a unique strain of mice found in Costa Rica called Scotinomys teguinawho are otherwise known as singing mice. They produce a high pitched singing noise, which can easily be mistaken for birdsong. The genes responsible for this unique behaviour are being used to study genes responsible for language in humans.

The gene researchers are interested in is called FOXP2. In humans, FOXP2 mutations lead to speech and language disorders. The FOXP2 gene encodes for a transcription factor, which controls the expression of other genes. Therefore, a mutation in the FOXP2 gene leads to the dysfunction of lots of other genes, which remain unknown.

This study found that neurons containing the FOXP2 gene became activated when songs from the same species were played. This shows the importance of FOXP2 in understanding vocal stimuli and the need for FOXP2 to interpret the information. The DNA from the mice is analysed and processed by a super computer to provide information on how FOXP2 plays a role in vocalisation. The importance of FOXP2 has been shown before by mice lacking the  FOXP2 gene by genetic modification, these mice show a lack of vocalisation.

Scotinomys teguin- the singing mouse from Costa Rica

So how can studying a gene in this exotic singing mouse contribute to medical research? If we can find out the role of FOXP2 in the singing mouse and its role in language, the information can be translated into humans to help cure speech disorders.

Further reading

Singing mouse video 

Function of FOXP2 in language disorders 

Can you hear me squeak?

Mice have been used in a study published in Neuron to show how gene therapy can be used to cure congenital hearing loss.  Congenital hearing loss affects 12,000 infants in the US every year.  It is a type of hearing loss that occurs at birth and is in the majority of cases is due to genetics and the loss of a crucial gene. At the moment, patients are treated with a hearing aid or in severe cases a cochlear implant, which can restore some hearing. However, a cure is yet to be found. This study looked at the possibility of using gene therapy to reverse genetic mutations and restore hearing loss.

This experiment used mice bred to lack an important gene required for hearing – the gene is called Vglut3, this gene produces a protein called vesicular glutamate transporter-3. This protein is required to allow the inner ear cells to transmit sound information to the brain. These mice were therefore born with hearing loss.

To correct the loss of the gene Vglut3 – a harmless virus containing a working copy of Vglut3 was injected into the ears of the mice the day after they were born. Two weeks later the hearing in treated mice was tested. The electrical properties of the cells in the ear was tested using electrophysiology. This test shows the function of the cells had been restored and allowed sound signals to be transmitted from the ear to the brain. The structure of the cells was also studied using electron microscopy, which allowed detailed analysis of the cells needed to allow successful transmission of sound signals. Both these tests showed that gene therapy had repaired the mutant cells and hearing had been restored in the mice

This is great news and very encouraging. The hope is that this can be translated into a clinical trial and a treatment for babies born with congenital hearing loss. Unfortunately, the mice used did not have the same genetic mutation as seen in humans, which the authors explain by the fact they only had access to these mice in their lab at the time of the experiment. Hopefully these positive results can be replicated in mice with the same genetic mutation as humans.

Further reading

Restoration of Hearing in the VGLUT3 Knockout Mouse Using Virally Mediated Gene Therapy – Neuron July 2012

Gene therapy to restore hearing sounds closer to reality after success in deaf-born mice – Spoonful of Medicine July 2012